Related Experiment Video
Updated: Nov 3, 2025
Visualization of SARS-CoV-2 using Immuno RNA-Fluorescence In Situ Hybridization
Published on: December 23, 2020
The Molecular Basis of COVID-19 Pathogenesis, Conventional and Nanomedicine Therapy
Shirin Kouhpayeh1, Laleh Shariati2,3, Maryam Boshtam4
1Erythron Genetics and Pathobiology Laboratory, Department of Immunology, Isfahan 8164776351, Iran.
Abstract:
In late 2019, a new member of the Coronaviridae family, officially designated as "severe acute respiratory syndrome coronavirus 2" (SARS-CoV-2), emerged and spread rapidly. The Coronavirus Disease-19 (COVID-19) outbreak was accompanied by a high rate of morbidity and mortality worldwide and was declared a pandemic by the World Health Organization in March 2020. Within the Coronaviridae family, SARS-CoV-2 is considered to be the third most highly pathogenic virus that infects humans, following the severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV). Four major mechanisms are thought to be involved in COVID-19 pathogenesis, including the activation of the renin-angiotensin system (RAS) signaling pathway, oxidative stress and cell death, cytokine storm, and endothelial dysfunction. Following virus entry and RAS activation, acute respiratory distress syndrome develops with an oxidative/nitrosative burst. The DNA damage induced by oxidative stress activates poly ADP-ribose polymerase-1 (PARP-1), viral macrodomain of non-structural protein 3, poly (ADP-ribose) glycohydrolase (PARG), and transient receptor potential melastatin type 2 (TRPM2) channel in a sequential manner which results in cell apoptosis or necrosis. In this review, blockers of angiotensin II receptor and/or PARP, PARG, and TRPM2, including vitamin D3, trehalose, tannins, flufenamic and mefenamic acid, and losartan, have been investigated for inhibiting RAS activation and quenching oxidative burst. Moreover, the application of organic and inorganic nanoparticles, including liposomes, dendrimers, quantum dots, and iron oxides, as therapeutic agents for SARS-CoV-2 were fully reviewed. In the present review, the clinical manifestations of COVID-19 are explained by focusing on molecular mechanisms. Potential therapeutic targets, including the RAS signaling pathway, PARP, PARG, and TRPM2, are also discussed in depth.
Insights
This review explores COVID-19 pathogenesis, detailing molecular mechanisms like RAS activation and oxidative stress. It examines potential therapeutics targeting these pathways and nanoparticles for SARS-CoV-2 treatment.
Area of Science:
- Virology and Molecular Biology
- Immunology
- Pharmacology
Background:
- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a global pandemic (COVID-19) with high morbidity and mortality.
- SARS-CoV-2 is the third most pathogenic human coronavirus after SARS-CoV and MERS-CoV.
- COVID-19 pathogenesis involves renin-angiotensin system (RAS) activation, oxidative stress, cytokine storm, and endothelial dysfunction.
Purpose of the Study:
- To elucidate the molecular mechanisms underlying COVID-19 clinical manifestations.
- To identify and discuss potential therapeutic targets for SARS-CoV-2 infection.
- To review therapeutic agents, including RAS blockers and nanoparticles, for COVID-19 treatment.
Main Methods:
- Review of scientific literature on COVID-19 pathogenesis and molecular mechanisms.
- Analysis of the roles of RAS, oxidative stress, PARP, PARG, and TRPM2 in disease progression.
- Investigation of therapeutic strategies targeting identified molecular pathways and nanoparticle-based treatments.
Main Results:
- Oxidative stress following RAS activation leads to DNA damage, activating PARP-1, PARG, and TRPM2, resulting in cell death.
- Blockers of angiotensin II receptor, PARP, PARG, and TRPM2 show potential in inhibiting RAS and oxidative burst.
- Various organic and inorganic nanoparticles have been reviewed for their therapeutic potential against SARS-CoV-2.
Conclusions:
- Understanding COVID-19 molecular mechanisms is crucial for developing effective treatments.
- Targeting the RAS pathway, PARP, PARG, and TRPM2 presents promising therapeutic avenues.
- Nanoparticle-based therapies offer a novel approach for managing SARS-CoV-2 infections.
More Related Videos
08:41Live Imaging and Quantification of Viral Infection in K18 hACE2 Transgenic Mice Using Reporter-Expressing Recombinant SARS-CoV-2
Published on: November 5, 2021
08:07A "Plug-And-Display" Nanoparticle Vaccine Platform Based on Outer Membrane Vesicles Displaying SARS-CoV-2 Receptor-Binding Domain
Published on: July 25, 2022
Related Concept Videos
01:29Microorganisms in Medicine and Therapeutics
02:50Conjugated Proteins
Nucleoproteins are protein complexes that contain nucleic acids, categorized as deoxyribonucleoproteins (DNPs) or ribonucleoproteins (RNPs) respectively. The nucleosome is a typical example of a DNP where nuclear DNA is associated with histone proteins. The major antigen for the Covid-19 virus SARS-CoV is an RNP that is critical...
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
02:49Cancer Therapies
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...
02:50Combination Therapies and Personalized Medicine
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
02:30siRNA - Small Interfering RNAs
In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by the...